CineECG analysis of body surface potential mapping performed in preclinical and clinical plakophilin-2-variant carriers

Abstract

Abstract Background/introduction Pathogenic variation of the plakophilin-2 (PKP2) gene is associated with arrhythmogenic cardiomyopathy (ACM). Disease manifestation in PKP2-pathogenic variant (PV) carriers differs greatly. Early detection of disease is crucial and could be of benefit in the risk stratification of this population. 67-lead body surface potential mapping (BSPM) could offer more insight into subtle electrical abnormalities. CineECG is a novel tool which can provide an estimation of the average pathway of ventricular activation based on the BSPM-signals, and could be of added value in the detection of electrical abnormalities. Purpose This study aimed to analyze 67-lead BSPM data with CineECG to ascertain the electrical activation pathway in PKP2-PV carriers and to compare these to the normal CineECG. Methods Ten PKP2-PV carriers underwent 67-lead BSPM. Six carriers were without definite ACM diagnosis (preclinical); no Task Force Criteria (TFC) were met apart from the identification of the pathogenic PKP2-variant. The other four carriers were all diagnosed with definite ACM (symptomatic). The average location and direction of ventricular activation was determined with CineECG, resulting in a CineECG trajectory throughout the ventricles. These results were compared to the normal CineECG trajectory, which was established in a previous study with normal ECG’s from the PTB-XL database. A CineECG trajectory that deviated more than 15% from the normal trajectory was considered abnormal. Additionally, to further determine the added diagnostic value of BSPM and CineECG beyond the standard 12-lead ECG, the 12-lead ECG’s were evaluated for abnormalities by three different ECG-experts. Results Expert evaluation of the 12-lead ECG showed that all preclinical PKP2-PV carriers had a normal ECG (no TFC and no other abnormalities such as abnormal electrical heart axis, pathological Q-waves or low voltage). In the symptomatic carriers, all ECG’s showed either presence of TFC or conduction abnormalities. Of the ten PKP2-PV carriers, eight exhibited an abnormal CineECG trajectory. In the preclinical group, four out of six carriers had an abnormal activation trajectory, while all symptomatic carriers had an abnormal CineECG trajectory. Conclusions Through CineECG analysis of 67-lead BSPM, abnormal ventricular activation was identified in the majority of PKP2-PV carriers. Notably, abnormal activation was observed in four out of six preclinical PKP2-PV carriers while the standard 12-lead ECG showed no abnormalities. Future research in a larger group, which also includes follow-up data, is warranted to determine whether these results are an indication of early signs of disease.Figure 1